Molecular forces, solvation, and controlled molecular interactions that result from these forces are the source of the astounding microscopic order and chemical reaction control that characterize cellular phenomena. The long range goal of this work is to answer significant questions about intermolecular and intramolecular force and to contribute to our general knowledge of molecular forces and aggregation phenomena in aqueous media and in less polar environments. We are particularly interested in physical aspects of the selective recognition of bioactive lipids, small carbohydrates, and aromatic aminoacid side chains. This is a project to study the chemistry of organic molecules that aggregate or fold due to functional group interactions and to study the binding properties and catalytic potential of such systems. The model systems in these projects are chosen based on their relevance to molecular interactions observed in biological systems. New knowledge and useful new data are expected. New generalizations and correlations among observations should arise during these studies and be available to scientists working in the medical and biochemical fields. Quantitative information obtained in this project will be useful to theoreticians for testing and refining chemical computational methods. The development of new catalytic systems or separation technologies may be stimulated by publication of the results expected in this project. Our goals are divided into three subprojects: A. Prepare simple model receptors and a "molecular torsion balance" to provide experimental data on weak intermolecular forces important to biological processes. Edge-face aromatic interactions, cation-aromatic interactions, and context dependence of hydrogen bonding will be studied. B. Investigate the aqueous-based model receptors for alicyclic and aromatic molecules that have been developed in the previous funding period. Prepare a new simpler water soluble cyclophane that will show high enantioselectivity in a 1:1 binding motif and measure its binding free energy with several enantiomeric guests. Use the knowledge gained to explore how hydrogen bonds and lipophilic contacts can combine to create self assembling termolecular structures. We will measure how delta-H, delta-S, and delta-Cp are affected by shape of substrate, shape of host, lipophilic surface contact area, and examine the effects of polar groups adjacent to the lipophilic surface. Isoprene derived subsubstrates and carbohydrates are to be targeted. The catalytic potential of these receptors will be tested. C. Continue the development of our carboxylic acids encased in a structurally restricted chiral alicyclic environment. These are the first examples of chirally encased acids and their carboxylates bind strongly to ureas. The enantioselectivity of these unique receptors will be studied. The acids may function as enantioselective proton sources and catalysts.